High-Frequency Stimulation Produces a Transient Blockade of
Voltage-Gated Currents in Subthalamic Neurons
CORINNE BEURRIER,1 BERNARD BIOULAC,1 JACQUES AUDIN,1 AND CONSTANCE HAMMOND2
1
Laboratoire de Neurophysiologie, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5543, Université
Bordeaux II, 33076 Bordeaux Cedex; and 2Institut National de la Santé et de la Recherche Médicale U29, 13273 Marseille
Cedex 09, France
Received 8 June 2000; accepted in final form 22 December 2000
pallidus internal part (EP/GPi)] as observed in 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and
naive rats (Benazzouz et al. 1995; Burbaud et al. 1994; Hayase
et al. 1996). It has also been suggested that the consequence of
clinical HFS will be to somehow counteract the abnormal
bursting pattern recorded in the STN in animal models of
Parkinson disease (Bergman et al. 1994; Hassani et al. 1996;
Hollerman and Grace 1992; Vila et al. 2000).
To understand the contribution of HFS in pathological conditions, it is clearly essential to determine whether a HFS of the
STN could modify or block the intrinsic activities of STN
neurons and to analyze the underlying mechanisms. This is
best achieved in vitro, as slice preparations enable to better
isolate the various effects of a tetanus on neuronal properties.
In the present study, using patch-clamp recordings of rat STN
neurons in slices, we report that HFS of the STN suppresses the
spontaneous activity of both single-spike and bursting STN
neurons. The effects of HFS are synaptic-independent and are
mediated by a blockade of the voltage-gated currents and
particularly the persistent Na⫹ (INaP) current and the L- and
T-type Ca2⫹ currents (ICaL and ICaT) that are known to generate
the intrinsic spontaneous discharge modes of STN neurons
(Beurrier et al. 1999, 2000; Bevan and Wilson 1999).
METHODS
Slice preparation
INTRODUCTION
The observation that deep brain stimulation applied at a
high-frequency (HFS) in the subthalamic nucleus (STN) and its
surgical destruction, both greatly ameliorate motor signs of
Parkinson’s disease in patients, led to the hypothesis that HFS
blocks, partly or completely, the activity of STN neurons. In
keeping with this, HFS in the STN has been shown to significantly decrease the frequency of extracellularly recorded STN
neurons in rats in vivo (Benazzouz et al. 1997). As STN
neurons are glutamatergic excitatory output neurons (Hammond et al. 1978; Robledo and Féger 1990; Smith and Parent
1988), the immediate consequence of their reduction of activity
could be the decrease of activity in target nuclei [substantia
nigra pars reticulata (SNr) and entopeduncular nucleus/globus
Address for reprint requests: C. Hammond, INSERM U29, Route de Luminy,
13273 Marseille Cedex 09, France (E-mail: [email protected]).
www.jn.physiology.org
Experiments were performed on STN neurons in slices obtained
from 20- to 28-day-old male Wistar rats. Rats were anesthetized with
ether and decapitated. The brain was quickly removed, and a block of
tissue containing the STN was isolated on ice in a 0 –5°C oxygenated
solution containing (in mM) 1.15 NaH2 PO4, 2 KCl, 26 NaHCO3, 7
MgCl2, 0.5 CaCl2, 11 glucose, and 250 saccharose, equilibrated with
95% O2-5% CO2 (pH 7.4). This cold solution, with a low NaCl and
CaCl2 content, improved tissue viability. In the same medium, 300- to
400-␮m-thick coronal slices were prepared using a vibratome (Campden Instruments, Loughborough, UK) and were then incubated at
room temperature in a Krebs solution containing (in mM) 124 NaCl,
3.6 KCl, 1.25 N-[2-hydroxyethyl]piperazine-N⬘-[2-ethanesulfonic
acid] (HEPES), 26 NaHCO3, 1.3 MgCl2, 2.4 CaCl2, and 10 glucose,
equilibrated with 95% O2-5% CO2 (pH 7.4). After a 2-h recovery
period, STN slices were transferred individually to an interface-type
The costs of publication of this article were defrayed in part by the payment
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0022-3077/01 $5.00 Copyright © 2001 The American Physiological Society
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Beurrier, Corinne, Bernard Bioulac, Jacques Audin, and Constance Hammond. High-frequency stimulation produces a transient
blockade of voltage-gated currents in subthalamic neurons. J Neurophysiol 85: 1351–1356, 2001. The effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) was analyzed with
patch-clamp techniques (whole cell configuration, current- and voltage-clamp modes) in rat STN slices in vitro. A brief tetanus, consisting of 100-␮s bipolar stimuli at a frequency of 100 –250 Hz during 1
min, produced a full blockade of ongoing STN activity whether it was
in the tonic or bursting mode. This HFS-induced silence lasted around
6 min after the end of stimulation, was frequency dependent, could be
repeated without alteration, and was not synaptically induced as it was
still observed in the presence of blockers of ionotropic GABA and
glutamate receptors or in the presence of cobalt at a concentration
(2 mM) that blocks voltage-gated Ca2⫹ channels and synaptic transmission. During HFS-induced silence, the following alterations were
observed: the persistent Na⫹ current (INaP) was totally blocked (by
99%), the Ca2⫹-mediated responses were strongly reduced including
the posthyperpolarization rebound (⫺62% in amplitude) and the plateau potential (⫺76% in duration), suggesting that T- and L-type
Ca2⫹ currents are transiently depressed by HFS, whereas the Cs⫹sensitive, hyperpolarization-activated cationic current (Ih) was little
affected. Thus a high-frequency tetanus produces a blockade of the
spontaneous activities of STN neurons as a result of a strong depression of intrinsic voltage-gated currents underlying single-spike and
bursting modes of discharge. These effects of HFS, which are completely independent of synaptic transmission, provide a mechanism
for interrupting ongoing activities of STN neurons.
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C. BEURRIER, B. BIOULAC, J. AUDIN, AND C. HAMMOND
recording chamber, maintained at 30 ⫾ 2°C (mean ⫾ SD) and
continuously superfused (1–1.5 ml/min) with the oxygenated Krebs
solution.
STN stimulation
The stimulating electrode was positioned in the middle of the STN
identified as an ovoid structure just lying at the border of the basal part of
the cerebral peduncle. Two types of stimulating electrodes were tested:
The bipolar concentric electrode measuring 0.5 mm in diameter (NEX100, Rhodes Medical Instruments) used by Burbaud (Burbaud et al.
1994) and Benazzouz (Benazzouz et al. 1995) for the in vivo stimulation
of the rat STN and a much thinner electrode (0.01 mm in diameter) that
we designed to avoid any mechanical lesion of the STN.
Electrophysiological recordings
Reagents
Drugs were applied by bath. Reagents were procured from Sigma
(St. Louis, MO), except 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX),
D-(⫺)-2-amino-5-phosphopentanoic acid (D-APV), and bicuculline,
which were purchased from Tocris (Bristol, UK).
Data analysis
Membrane potential was recorded using Axoclamp 2A or Axopatch
1D amplifier (Axon Instruments, Foster City, CA), displayed simultaneously on a storage oscilloscope and a four-channel chart recorder
(Gould Instruments, Longjumeau, France), digitized (DR-890, NeuroData Instruments, New York), and stored on a videotape for subsequent off-line analysis. During voltage-clamp recordings, membrane
currents were fed into an A/D converter (Digidata 1200, Axon Instruments), stored, and analyzed on a PC using pCLAMP software (version 6.0.3, Axon Instruments). Corrections for the liquid junction
potential were performed according to Neher (1992): ⫺6 mV for the
K-gluconate-based pipette solution as estimated with a 3 M KCl
ground electrode.
RESULTS
HFS-induced arrest of single-spike or bursting activity
STN activity was recorded in current-clamp mode (whole
cell configuration) for at least 1 min before the HFS was
applied. Using a bipolar concentric stimulating electrode similar to that used in rat in vivo (see METHODS), a brief (1 min)
HFS consisting of 100 ␮s stimuli of 5– 8 V amplitude, produced a blockade of ongoing activity whether it was in singlespike (Fig. 1) or bursting (Fig. 2) mode. This effect was
frequency dependent (Figs. 1A and 2) with an optimal frequency of 166 up to 250 Hz that produced a full blockade of
the activity (n ⫽ 17). The latency of the HFS-induced silence
could not be determined in detail as during the 1-min stimu-
FIG. 1. Effect of high-frequency stimulation (HFS) on the spontaneous
single-spike activity of 2 subthalamic nucleus (STN) neurons. A: frequency
dependence of HFS. Applied at 100 Hz, HFS had nearly no posteffect whereas
at 125 Hz it decreased the frequency of tonic activity and at 166 Hz stopped
single-spike activity for 5 min. B: continuous chart recording (top) at slow time
resolution of the activity of an other STN neuron. HFS (250 Hz) stopped
single-spike activity at a potential of ⫺51 mV for 1 min 12 s. Symbols indicate
the parts of the top recording that are shown at an expanded time scale in
bottom traces.
lation period, artifacts prevented analysis of the activity. Nevertheless as shown in Figs. 1B and 2, above a certain frequency, the onset of the blockade was immediately obvious by
the end of the train. Interestingly, HFS blocked both single
spike (Fig. 1) and burst firing (Fig. 2) modes, suggesting that
its mechanisms do not involve a current(s) that is expressed
only in one type of discharge.
The suppression of STN spontaneous activity was observed
for 5.8 ⫾ 0.7 min (range: 1.1–18.0, n ⫽ 31) after HFS. At the
end of the silence period, spontaneous activity slowly recovered in the same mode as before stimulation (Figs. 1B to 6).
During cell silence, membrane potential remained stable at
⫺52.2 ⫾ 0.8 mV (range: ⫺40 to ⫺68, n ⫽ 45) for tonic cells
and at ⫺56.2 ⫾ 1.4 mV (range: ⫺48 to ⫺61 mV, n ⫽ 8) for
bursting cells. These membrane potentials were significantly
more depolarized than the potentials at which cells were silent
in control conditions: before HFS, cells tested in the tonic
mode were silent at ⫺60.2 ⫾ 0.6 mV (range: ⫺49 to ⫺68 mV,
n ⫽ 45, P ⬍ 0.001, paired t-test) and cells tested in the bursting
mode were silent at ⫺63.5 ⫾ 1.3 mV (range: ⫺56 to ⫺68 mV,
n ⫽ 8, P ⫽ 0.015, paired t-test). This suggested that HFS did
not stop STN cell activity simply by transiently hyperpolarizing the membrane.
Spikes could still be evoked during the silence period in all
tested neurons (n ⫽ 60). However, in half of the cells, spike
threshold was significantly higher during the silence period
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Slices were visualized using a dissecting microscope and the recording electrode was precisely positioned in the STN. Electrophysiological recordings of STN neurons were performed in the current- or
voltage-clamp mode using the blind patch-clamp technique in the
whole cell configuration. Patch electrodes were pulled from filamented borosilicate thin-wall glass capillaries (GC150F-15, Clarck
Electromedical Instruments, Pangbourne, UK) with a vertical puller
(PP-830, Narishige, Japan) and had a resistance of 10 –12 M⍀ when
filled with the following (in mM): 120 Kgluconate, 10 KCl, 10 NaCl,
10 ethylene glycol-bis(b-aminoethyl ether)-N,N,N⬘,N⬘-tetraacetic acid
(EGTA), 10 HEPES, 1 CaCl2, 2 MgATP, and 0.5 NaGTP, pH 7.25.
HFS DEPRESSES STN VOLTAGE-GATED CURRENTS
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FIG. 4. HFS-induced silence is independent of ionotropic synaptic transmission. HFS (500 Hz) reversibly stopped single-spike activity of a STN
neuron for 8 min at ⫺45 mV (control). A 2nd HFS (500 Hz) was applied in the
continuous presence of D-APV, CNQX, and bicuculline (Bic). Single-spike
activity was stopped at ⫺45 mV for 9 min.
(⫺39.3 ⫾ 1.6 mV, n ⫽ 30) compared with the control
(⫺47.5 ⫾ 0.6 mV, n ⫽ 30, P ⬍ 0.001; Fig. 3). So was also
input membrane resistance, which was significantly increased
during HFS-induced silence, when tested at Vm ⫽ ⫺65 mV by
applying hyperpolarizing current pulses of ⫺100/-200 pA amplitude (247.2 ⫾ 21.1 vs. 226.1 ⫾ 16.3 M⍀, P ⫽ 0.035, n ⫽
20). A second tetanus, applied after the cell recovered from the
first one, reversibly silenced the cell again (n ⫽ 15). This could
be repeated as long as patch recording could last. Therefore
HFS does depress neuronal activity in slices, and this effect is
short lasting and can be repeated. In subsequent experiments,
we used a thinner electrode designed to avoid any mechanical
lesion of the STN. We chose to use the same parameters of
train duration (1 min) and of bipolar stimuli intensity (5– 8 V)
and duration (100 ␮s) but to vary their frequency in the train
(range 100 –500 Hz) to obtain a clear-cut suppression of activity during which a long-lasting analysis of currents or specific responses could be performed.
tions of ionotropic glutamate and GABAA receptor antagonists, CNQX (20 ␮M), D-APV (40 ␮M), and bicuculline (10
␮M) failed to prevent the effects of HFS (n ⫽ 6, Fig. 4).
Furthermore HFS still suppressed single-spike activity when
synaptic transmission was blocked by 2 mM Co2⫹ (n ⫽ 16,
Fig. 5A, top). Since the silencing effect of HFS did not require
Ca2⫹-dependent transmitter release, we tested whether it was
possible to mimic this effect with intracellular stimulation of
the recorded cell. When comparing the two types of HFS
(extracellular and intracellular) in the same tonically active
STN neurons (n ⫽ 8), it appeared that both HFS resulted in a
silence of the cell. However, intracellular HFS had a different
effect on membrane potential: there was a strong hyperpolarization of the membrane at the break of the intracellular pulses
(to ⫺63.2 ⫾ 3.1 mV) that declined in about 20 s to ⫺48.1 ⫾
4.1 mV, a potential at which tonic activity recovered (n ⫽ 8,
data not shown). Such an after hyperpolarization and slow
membrane repolarization were never observed after extracellular HFS where membrane potential remained stable during
cell silence (Figs. 1– 6).
HFS-induced suppression of activity is independent of
synaptic activity
An important issue was to determine whether effects of the
train were mediated by synaptic transmission. Bath applica-
⫹
FIG. 3. Increase of threshold potential for Na -dependent spikes during
HFS-induced silence. Chart recording at low time base of a tonic STN neuron
(top). HFS (250 Hz) stopped single-spike activity at a potential of ⫺48 mV for
1 min 25 s. Bottom: Na⫹-dependent spikes evoked by a depolarizing pulse of
100 ms, before HFS (a, 80 pA), during HFS-induced silence (b, 100 pA), and
after recovery of activity (c, 80 pA).
HFS-induced decrease of voltage-gated currents
We hypothesized that HFS induced a modification of voltage-sensitive currents essential for the expression of tonic and
burst-firing modes (Beurrier et al. 2000; Bevan and Wilson
1999). In the tonic mode, the silencing effect of HFS did not
require Ca2⫹ influx since it was still observed in the presence
of 2 mM Co2⫹ nor increase of intracellular Ca2⫹ concentration
since it was present in BAPTA-loaded cells (n ⫽ 4, data not
shown). We therefore tested the effect of HFS on spontaneous
tonic activity and INaP recorded from the same STN neurons by
shifting from current- to voltage-clamp mode before, during,
and after HFS-induced silence. In voltage-clamp mode, in
response to a voltage ramp and in the continuous presence of
Co2⫹, a TTX-sensitive inward current that had the characteristics of a persistent Na⫹ current was recorded. It was strongly
reduced during HFS-induced silence (Fig. 5). I-V relationships
before and during HFS-induced silence showed that peak amplitude of INaP was reduced by 99% during cell silence as
compared with the control (from ⫺122.2 ⫾ 13.1 to ⫺1.1 ⫾ 1.1
pA, n ⫽ 9; Fig. 5, B and C). This effect reversed to 78% of
control (to ⫺92.5 ⫾ 9.9 pA, n ⫽ 8) once cell activity recov-
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FIG. 2. Frequency-dependent effect of HFS on spontaneous bursting activity of a STN neuron. Chart recording at slow time base of a bursting STN
neuron (burst firing was evoked by continuous injection of ⫺150 pA). At 100
and 125 Hz, HFS decreased burst frequency (bottom traces) whereas at 166 Hz
it totally suppressed bursting activity for 1 min and 49 s. Activity then
recovered in burst firing mode. Symbols indicate the parts of the top recording
that are shown at an expanded time scale in bottom traces.
1354
C. BEURRIER, B. BIOULAC, J. AUDIN, AND C. HAMMOND
1119.4 ⫾ 150.6 to 425.6 ⫾ 111.4 ms, n ⫽ 32) sometimes with
a total suppression of the after spike depolarization (Fig. 6, A,
top and middle, and B, left). Concomitantly, the amplitude of
the rebound potential was reduced by 75.9% (from 8.8 ⫾ 0.4
to 2.1 ⫾ 0.5 mV, n ⫽ 23; Fig. 6, A, top and bottom, and B,
right). Once cell activity recovered, the effects on plateau
potential duration and on the amplitude of rebound potential
reversed to 66% of control (to 739.4 ⫾ 217.9 ms, n ⫽ 18) and
to 39% of control (to 3.4 ⫾ 0.8 mV, n ⫽ 14), respectively.
In contrast, the Cs⫹-sensitive, hyperpolarization-activated
cation current (Ih) was not affected by HFS at potentials
normally traversed by the membrane during tonic firing. It was
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⫹
FIG. 5. Effect of HFS on the persistent Na current in the absence of
synaptic transmission. A: HFS (500 Hz) applied in the continuous presence of
Co2⫹ (2 mM) stopped the activity of a tonically firing STN neuron (for 18 min
at ⫺60 mV; top). In response to a 5-mV/s depolarizing ramp from ⫺80 to ⫺10
mV, a slow inward current was recorded before HFS (a), 110 s after HFS (b,
during HFS-induced silence), and 36 min after HFS (c, after recovery of
activity). TTX (1 ␮M) applied at the end of the experiment totally abolished
the slow inward current as well as the fast ones (c, bottom). B: I-V relationships
of the persistent Na⫹ current obtained from the same cell in A. The curve
HFS-TTX represents the subtraction of traces Ab–Ac. The curve control-TTX
represents the subtraction of traces Aa–Ac. C: histogram of INaP peak amplitude before (control), during (HFS), and after (recovery) HFS-induced silence.
*, comparison with preceding column; E, comparison with control. * or E:
P ⬍ 0.05; **: P ⬍ 0.001; ***: P ⬍ 0.0001.
ered. When applied at the end of the experiment, TTX (1 ␮M)
totally blocked this current, confirming that it was INaP
(Fig. 5A).
Spontaneous bursting mode and ICa were then analyzed.
However, since the recording of Ca2⫹ currents requires the
presence of K⫹ channel blockers, a procedure incompatible
with the recording of burst firing in current-clamp mode, the
amplitude of Ca2⫹ currents was therefore evaluated from the
evoked potentials they underlie: the rebound depolarization,
also called low-threshold Ca2⫹ spike (LTS), that results from
the activation of a T-type Ca2⫹ current and the plateau potential that results from the combined action of the nifedipinesensitive L-type Ca2⫹ current and a Ca2⫹-activated inward
current (Beurrier et al. 1999). Following HFS, during minutes
of silence, plateau duration was reduced by 62% (from
2⫹
FIG. 6. Effect of HFS on Ca -mediated responses. A, top: HFS (500 Hz)
stopped the activity of a burst-firing STN neuron (at ⫺63 mV). Middle: plateau
potential triggered by a depolarizing current pulse at Vm ⫽ ⫺65 mV (⫹80 pA,
100 ms), lasted 760 ms before HFS (a), lasted 150 ms during cell silence (b,
70 s after HFS), and lasted 520 ms during recovery of bursting activity (c, 17
min after HFS). 2 indicates the after spike depolarization (ADP) present in a
and c and absent in b. Bottom: rebound potential (2) recorded at the break of
a hyperpolarizing pulse (⫺80 pA, 500 ms) had an amplitude of 10 mV before
HFS (a), of 2.5 mV during silence (b, 8 min 30 s after HFS), and of 5 mV after
recovery of bursting activity (c, 34 min after HFS). In the same traces, note the
absence of modification of the depolarizing sag that developed during the
current pulse. All recordings were obtained from the same STN neuron. B, left:
histogram of plateau potential duration before (control), during (HFS), and
after (recovery) HFS-induced silence. Right: histogram of rebound potential
amplitude before, during, and after HFS-induced silence. *, comparison with
preceding column; E, comparison with control. *P ⬍ 0.05; ** or E E: P ⬍
0.001; *** or E E E: P ⬍ 0.0001.
HFS DEPRESSES STN VOLTAGE-GATED CURRENTS
reduced between ⫺80 and ⫺110 mV (by 26.5% at ⫺90 mV,
n ⫽ 5, Fig. 7). Consistent with these findings on Ih, the
amplitude of the depolarizing sag observed during a hyperpolarizing current pulse was not significantly affected (it was
reduced by 4.8%, from 5.21 ⫾ 0.82 to 4.99 ⫾ 0.80 mV, P ⫽
0.69, n ⫽ 12; Fig. 6A, bottom).
DISCUSSION
Our results show that HFS blocks the spontaneous activity of
tonic and bursting STN neurons with a mechanism that does
not require Ca2⫹-dependent transmitter release. The silencing
effect of HFS has a short latency, is brief, reversible, can be
repeated several times with little change, and is frequency
dependent. It is mediated by a dramatic reduction of Na⫹ and
Ca2⫹ voltage-gated currents leading to an interruption of the
spontaneous activities of the neurons. In fact, in single-spike
activity, a TTX-sensitive, persistent Na⫹ current (INaP), underlies the slow pacemaker depolarization that spontaneously depolarizes the membrane from the peak of the after spike hyperpolarization to the threshold potential for spike initiation
(Beurrier et al. 2000; Bevan and Wilson 1999). In contrast, in
burst-firing mode, the interplay between a T-type Ca2⫹ current
(ICaT), an L-type Ca2⫹ current (ICaL), and a Ca2⫹-activated
inward current, all insensitive to TTX, underlie recurrent membrane oscillations (Beurrier et al. 1999). The blockade of these
subliminal currents can also explain the increase of membrane
resistance observed during HFS-induced silence.
The silencing effect of HFS does not result from the activation of a local network and is not mediated by the stimulation
of afferents to the STN, since it was still observed in the
presence of blockers of glutamatergic and GABAergic ionotropic synaptic transmission and in the presence of cobalt at a
concentration that totally blocked synaptic transmission in the
STN. It was in fact reproduced by direct stimulation of the
recorded STN cell as previously tested by Borde et al. (2000)
in hippocampal CA1 pyramidal neurons. In this preparation, a
low-frequency intracellular stimulation induced a depression of
activity that developed rapidly, was reversible, persisted up to
3 min and was still observed when synaptic transmission was
strongly reduced by the P-type Ca2⫹ channel blocker ␻-agatoxin IVA or enhanced by 4-aminopyridine. The insensitivity
of depression to synaptic blockade indicates little if any involvement of synaptic mechanisms and implies that postsynaptic mechanisms are key factors as observed in the present
study with extracellular HFS. However, mechanisms underlying intracellular stimulation may be different from those underlying extracellular HFS. The silencing effect of intracellular
stimulation is Ca2⫹-dependent since it requires Ca2⫹ influx and
intracellular Ca2⫹ increase in the stimulated cell (Borde et al.
2000), whereas that of extracellular HFS is Ca2⫹-independent
(the present study).
As the pattern of discharge of STN neurons may play an
important role in the physio-pathology of parkinsonism (Bergman et al. 1994; Hollerman and Grace 1992), it is tempting to
correlate the present effects of in vitro HFS on the spontaneous
STN activity, to the beneficial effects of high-frequency deep
brain stimulation in the STN of MPTP-treated monkeys
(Benazzouz et al. 1992; Hayase et al. 1996) or parkinsonian
patients (Benabid et al. 1994; Limousin et al. 1998). However,
such a direct correlation needs further experiments. First, clinical HFS is performed in vivo where it could affect the whole
basal ganglia network, at least at the onset of stimulation.
Second, clinical HFS is efficient at lower frequencies (125–185
Hz) than sometimes in vitro HFS does. This could be explained
by the differences in the characteristics of the stimulating
electrode. Finally, beneficial clinical effects are observed during the continuous application of the stimulation and only for
a short while after the stimulation, whereas in the present
study, only events that followed the stimulation have been
studied. Nevertheless, the present results give some insights in
the way intrinsic activity of STN neurons can be depressed.
Present address of C. Beurrier: Dept. of Psychiatry and Behavioral Sciences,
School of Medicine, Stanford University, 1201 Welch Rd., Palo Alto, CA
94304-5485.
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FIG. 7. Effect of HFS on the hyperpolarization-activated cation current Ih.
Left: from a holding potential of ⫺50 mV, a family of currents was evoked in
response to 1,500-ms hyperpolarizing steps from ⫺60 to ⫺110 mV (10-mV
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Right: I-V relationship of Ih before (control), during HFS-induced silence
(HFS), and in the presence of 1–3 mM cesium in the bath (VH ⫽ ⫺50 mV).
Values of I were obtained by subtracting the value of the current at the
beginning of the hyperpolarizing pulse from that at the end of the pulse.
Currents were normalized (I/Imax) to the maximal current (Imax) recorded at
⫺110 mV.
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